目的：评价自体树突状细胞 (dendritic cell, DC) 联合细胞因子诱导的杀伤(cytokine-induced killer, CIK) 细胞治疗晚期结直肠癌患者的临床疗效和安全性。方法： 采集2011年7月至2015年3月解放军第81医院肿瘤生物治疗科收治的142例Ⅲ~Ⅳ期结直肠癌患者的外周血单个核细胞 (peripheral blood mononuclear cell, PBMC)，经实验室体外诱导培养DC和CIK细胞。DC细胞通过结肠癌细胞株COLO 320或直肠癌细胞株HCT-116裂解物致敏后与CIK细胞回输至结直肠癌患者，观察DC-CIK细胞治疗的临床疗效和安全性。结果： 142例晚期结直肠癌患者经DC-CIK细胞免疫治疗后，客观缓解率为162%，疾病控制率为60.6%；1年生存率为47%，2年生存率为31%，3年生存率为31%；经细胞治疗后外周血CD3+T细胞、CD4+T细胞、CD8+T细胞、CD3+CD56+ NK细胞、CD4+CD25+ Treg细胞比例、CD4+/CD8+比值及癌胚抗原(carcinoembryonic antigen, CEA) 水平均无显著变化；单因素分析显示，TNM分期 (P=0.015)、治疗次数 (P=0.037) 及治疗前CEA值的正常与否为DC-CIK治疗结直肠癌的预后影响因素；多因素分析显示，治疗次数 (P=0.024) 和年龄 (P=0.015) 与DC-CIK治疗结直肠癌的预后密切相关。结论： DC-CIK细胞免疫治疗可能改善晚期结直肠癌患者远期生存率，可产生临床获益，无明显不良反应，安全可行。

Objective:To evaluate the safety and efficacy of combination therapy with dendritic cells (DCs) and cytokine-induced killer (CIK) cells in the treatment of advanced colorectal cancer (CRC). Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 142 patients with stage Ⅲ~Ⅳ CRC who were admitted to the Tumor Biotherapy Center of the No. 81 Hospital of PLA in Nanjing from August, 2011 to December, 2014. The cells were cultured ex vivo to generate DC and CIK cells. After sensitized with cell lysates from colon cancer cells Colo-320 or rectal cancer cells HCT-116, the DCs were transfused to CRC patients after combined with the CIK cells. T-lymphocyte subsets, serum CEA level, and clinical features were evaluated before and after the combined DC and CIK treatment. Results: Following the combined DC and CIK immunotherapy in patients with advanced CRC for 40 months, the overall response rate was 162%, the disease control rate was 60.0%, one-year overall survival rate was 47%, and both two-year and three-year overall survival rate was maintained at 31%. No significant alterations in T-lymphocyte subsets, CD4+/CD8+ ratio, and CEA level were found in these patients after the combination therapy. Single-factor analysis indicated that tumor stage (P=0.015), the frequency of immunotherapy (P=0.037), and CEA value (P=0.037) affected significantly the survival period of these CRC patients. Multivariate Cox model indicated that frequency of the combined DC and CIK immunotherapy (P=0.024) and age (P=0.015) associated significantly with the risk of cancer-related death in these CRC patients. Conclusion: The combined autologous DC/CIK immunotherapy is a safe and feasible therapeutic approach and it may improve the long-term survival rate in patients with stage Ⅲ~Ⅳ CRC.

南京军区医学科技创新项目资助（No. 14MS052)